Abstract
In assessing species susceptibility for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and in the search for an appropriate animal model, multiple research groups around the world inoculated a broad range of animal species using various SARS-CoV-2 strains, doses and administration routes. Although in silico analyses based on receptor binding and diverse in vitro cell cultures were valuable, exact prediction of species susceptibility based on these tools proved challenging. Here, we assessed whether precision-cut lung slices (PCLS) could facilitate the selection of animal models, thereby reducing animal experimentation. Pig, hamster and cat PCLS were incubated with SARS-CoV-2 and virus replication was followed over time. Virus replicated efficiently in PCLS from hamsters and cats, while no evidence of replication was obtained for pig PCLS. These data corroborate the findings of many research groups that have investigated the susceptibility of hamsters, pigs and cats towards infection with SARS-CoV-2. Our findings suggest that PCLS can be used as convenient tool for the screening of different animal species for sensitivity to newly emerged viruses. To validate our results obtained in PCLS, we employed the hamster model. Hamsters were inoculated with SARS-CoV-2 via the intranasal route. Susceptibility to infection was evaluated by body weight loss, viral loads in oropharyngeal swabs and respiratory tissues and lung pathology. The broadly used hamster model was further refined by including activity tracking of the hamsters by an activity wheel as a very robust and sensitive parameter for clinical health. In addition, to facilitate the quantification of pathology in the lungs, we devised a semi-quantitative scoring system for evaluating the degree of histological changes in the lungs. The inclusion of these additional parameters refined and enriched the hamster model, allowing for the generation of more data from a single experiment.
Highlights
In December 2019, the first cases of atypical pneumonia associated with infection by a novel coronavirus (CoV) were reported in China [1]
To tackle the initial lack of animal models, to minimize the ethical concerns of using irrelevant animal species and to reduce the number of animals used for the development of models, we evaluated the use of precision-cut lung slices (PCLS) as an ex vivo model to predict the susceptibility of different animal species to infection with SARS-CoV-2
Next-generation sequencing (NGS) results confirmed the absence of adventitious agents and showed that the consensus sequences of the two passages were 100% identical and that no low abundance mutations were present in the viral spike protein
Summary
In December 2019, the first cases of atypical pneumonia associated with infection by a novel coronavirus (CoV) were reported in China [1]. Sequence analysis of the new CoV revealed a close phylogenetic relationship to SARS-CoV (Severe Acute Respiratory Syndrome Coronavirus)-like bat CoV strains [2,3]. The new CoV was officially named SARS-CoV-2 [4]. In 2012, another CoV emerged in Saudi Arabia, named Middle East Respiratory Syndrome (MERS)-CoV. MERSCoV causes sporadic cases of a severe respiratory syndrome and outbreaks in healthcare settings [6]. Both viruses are suspected to originate from bats and to have acquired adaptations that allow transmission to other species [7]. Different animal species may play a role in future coronavirus outbreaks and can be used as suitable models for studying the infection, transmission and pathogenesis of the corresponding viruses
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